t(2;11)(q31;p15) in therapy related myeloid neoplasm: case report and review of literature

Amarpreet Bhalla, Anwar N Mohamed  

Cytogenetics Laboratory, Pathology Department, Wayne State University School of Medicine, Detroit Medical Center, Detroit MI, USA

Previous history

Malignant disease
Inborn condition
Main items
+ Patient diagnosed with breast cancer in 1995, treated with adjuvant chemotherapy consisting of 4 cycles of CAF (cyclophosphamide, doxorubicin and fluorouracil) and CMF (cyclophosphamide, methotrexate and fluorouracil) followed by tamoxifen for 6 years. On 6/2006, she had evidence of recurrence and subsequent liver, ribs, and skull metastases. She was treated with several other chemotherapies such as taxotere, gemzar, fluvestrant, taxol, bevacizumab and xeloda, and radiation therapy. On 11/2011, she developed brain metastasis and was successfully treated with gamma knife. Over her last year, she was on oral cyclophosphamide and doxorubicin.
Family History: Sister with brain tumor and brother with colon cancer.

Clinics case report

59 yrs
Lymph nodes
Cns involv
+ brain metastasis

Blood data

Bone marrow biopsy revealed a hypercellular marrow with 80% cellularity, multilineage dysplasia, 10.2% immature monocytes and 3.2% myeloblasts. CD34/CD117 showed approximately 10% immature myeloid/monocytic cells. CD64 highlighted the expanded monocytic component. In addition there were scattered metastatic tumor cells positive for AE1/AE3, mammoglobin and BRST1 by immunohistochemistry supporting primary breast origin.

Cyto path

Therapy related myeloid neoplasm best classified as therapy related myelodysplastic /acute myeloid leukemia (t-MDS/AML).
Flow cytometric of peripheral blood detected 2% myeloblasts expressing CD13, CD33, CD 34, CD117 and HLA-DR, and partially expressing CD14, CD4, CD11d, CD11c and CD64. In addition there were two monocytes gates detected; 18% monocytes were expressing CD13, CD33, and partially expressing CD4, CD11b, CD11c, CD15, CD117, CD64 and CD14. There was a subpopulation of monocytes representing 6% of gated monocytes were negative CD14, CD19, CD2, CD10, CD7, CD34, CD163 but HLA-DR positive.
Rearranged ig tcr
Not performed.
Electron microscopy
Not performed.
Precise diagnosis
Therapy related MDS/AML

Survival data

Date diagnosis
Only supportive therapy
Complete remission
Treatment relat death
Date last follow
Progressed quickly, expired shortly after diagnosis due to lactic acidosis and hypotention


Bone marrow aspirate
Culture time
24 unstimulated culture and 48 hrs culture with 10% conditioned medium
46, XX,t(2;11)(q31;p15)[14]/47,XX,t(2;11)(q31;p15),+8[6] (Figure 1)

Other molec studies

In addition, dual color FISH using Signature Genomic DNA probes Rp11-387A1/2q31.1 covering HOXD gene cluster including both HOXD11 and HOXD13 genes was labeled SpectrumOrange, while the RP11-120E20/11p15.4 covering NUP98 gene was labeled SpectrumGreen (PerkinElmer, Spokane, WA). The hybridization revealed a fusion signal located on der(2) due to a translocation of NUP98/15p15 (green) to HOXD/2q31(orange) gene region (Figure 2). The remainder of HOXD signal was translocated to 11p15.


Atlas Image
Figure 1: G-banded karyotype showing t(2;11)(q31;p15) (arrows).
Atlas Image
Figure 2: Dual color FISH analysis performed on a metaphase with t(2;11) using BAC probes for NUP98 (RP11-120E20) labeled in green and for HOXD (RP11387A1) labeled in orange, showed the presence of a fusion signal on der(2) (arrow); two orange signals on der(11) and chromosome 2; single green on normal chromosome 11.
Atlas Image
Table 1: Leukemia cases with t(2;11)(q31;p15) previously reported and the present case. Y: Years; Mon: Months; F: Female; M: Male.

Comments section

In Summary, t(2;11)(q31;p13) translocation in leukemia is rare but recurrent, and occurs in de novo AML as well as t-MDS/AML, and six out eight of patients were <15 years including three infants (Table 1). Morphologically this translocation appears to be associated with monocytic features, mostly AML M4. The t(2;11) leads to the generation of leukemogenic NUP98 fusion protein.


Pubmed IDLast YearTitleAuthors
97666501998NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.Raza-Egilmez SZ et al
109950092000Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation.Arai Y et al
109310002000Generation of the NUP98-HOXD13 fusion transcript by a rare translocation, t(2;11)(q31;p15), in a case of infant leukaemia.Shimada H et al
117823542002The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15).Taketani T et al
153901872004Analysis of translocations that involve the NUP98 gene in patients with 11p15 chromosomal rearrangements.Kobzev YN et al
157558992005NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia.Lin YW et al
176562572007A complex karyotype, including a three-way translocation generating a NUP98-HOXD13 transcript, in an infant with acute myeloid leukemia.Hidaka E et al
214942612011Backtracking to birth of the NUP98-HOXD13 gene fusion in an infant acute myeloid leukemia.Emerenciano M et al


Amarpreet Bhalla, Anwar N Mohamed

t(2;11)(q31;p15) in therapy related myeloid neoplasm: case report and review of literature

Atlas Genet Cytogenet Oncol Haematol. 2013-06-01

Online version: http://atlasgeneticsoncology.org/case-report/208868/t(2;11)(q31;p15)-in-therapy-related-myeloid-neoplasm-case-report-and-review-of-literature